Peptides representing epitopic sites for bacterial and viral meningitis causing agents and their CNS carrier and uses thereof

Abstract

Peptides comprising a Meningitis Related Homologous Antigenic Sequence (MRHAS) are provided. The MRHAS is found in meningitis-causing organisms and chemokines involved in cell chemotaxis. The peptides are useful as antigens and vaccines for detection, diagnosis and treatment of meningitis.

We claim: 
     
       1. A peptide having the formula   aXb,     wherein   a is linked to X by a simple peptide bond and b is linked to X by a simple peptide bond,   wherein X is a Meningitis Related Homologous Antigenic Sequence contained in the amino acid sequence of a protein or peptide found in a bacterium or virus that is an etiologic agent of meningitis, said protein or peptide is a chemokine involved in cell chemotaxis, and wherein said Meningitis Related Homologous Antigenic Sequence is at least 7 sequential amino acids and conservative substitutions or modifications thereof selected from the group consisting of: (i) the amino acid sequence of the Structural Polyprotein of a strain of Rubella virus that corresponds to AA 102  -AA 108  of said protein of the M33 strain of Rubella virus as set forth in SEQ ID NO:1;   (ii) the amino acid sequence of the Structural Polyprotein of a strain of Rubella virus that corresponds to AA 89  -AA 95  of said protein of the M33 strain of Rubella virus as set forth in SEQ ID NO:1;   (iii) the amino acid sequence of the Structural Polyprotein of a strain of Rubella virus that corresponds to AA 313  -AA 319  of said protein of the M33 strain of Rubella virus as set forth in SEQ ID NO:1;   (iv) the amino acid sequence of the Structural Polyprotein of a strain of Rubella virus that corresponds to AA 103  -AA 109  of said protein of the Therien strain of Rubella virus as set forth in SEQ ID NO:8;   (v) the amino acid sequence of the Structural Polyprotein of a strain of Rubella virus that corresponds to AA 90  -AA 96  of said protein of the Therien strain of Rubella virus as set forth in SEQ ID NO:8;   (vi) the amino acid sequence of the Structural Polyprotein of a strain of Rubella virus that corresponds to AA 314  -AA 320  of said protein of the Thorion strain of Rubella virus as set forth in SEQ ID NO:8;   (vii) the amine acid sequence of the Gag Polyprotein of an isolate of the HIV-1 that corresponds to AA 145  -AA 151  of the Gag Polyprotein of the LV isolate of HIV-1 as set forth in SEQ ID NO:11;   (viii) the amine acid sequence of the Envelope Polypretain Precursor of an isolate of the HIV-1 that corresponds to AA 655  to AA 661  of the Envelope Polypretain Precursor of the LAV-1a isolate of HIV-1 as set forth in SEQ ID NO:14;   (ix) the amine acid sequence that corresponds to AA 99  -AA 105  of the Lipoprotein E Precursor of Haemophilus influenzae as set forth in SEQ ID NO:17;   (x) the amine acid sequence that corresponds to AA 1  to AA 5  of the Opacity-Related Protein POPM3 of Neisseria meningitidis as set forth in SEQ ID NO:20;   (xi) the amine acid sequence that corresponds to A 123  to AA 129  of the Pneumococcal Surface Protein A of Streptococcus pneumoniae as set forth in SEQ ID NO:23;   (xii) the amine acid sequence that corresponds to AA 151  -AA 157  of the Protein P60 Precursor of Listeria monocytogenes as set forth in SEQ ID NO:26;   (xiii) the amine acid sequence that corresponds to AA 181  -AA 187  of the Protein P60 Precursor of Listeria monocytogenes as set forth in SEQ ID NO:26;   (xiv) the amine acid sequence that corresponds to AA 249  -AA 255  of the Protein P60 Precursor of Listeria monocytogenes as set forth in SEQ ID NO:26;   (xv) the amine acid sequence that corresponds to A 292  -AA 298  of the Protein P60 Precursor of Listeria monocytogenes as set forth in SEQ ID NO:26;   (xvi) the amine acid sequence of a variant of the chemokine human Monocyte Chemoattractant Factor hMCP-1, that corresponds to AA 93  -AA 99  of hMCP-1 as set forth in SEQ ID NO:35; and   (xvii) the amino acid sequence of the chemokine hMCP-3, that corresponds to AA 61  -AA 67  of hMCP-3 as set forth in SEQ ID NO: 38,       wherein a is an amino terminus which comprises (i) one to eight sequential amino acids from the native amino acid sequence of the protein immediately N-terminal to said X, or conservative substitutions in or modifications of said native amino acid sequence or   (ii) a substituent effective to facilitate coupling of the peptide to another moiety       and wherein b is a carboxy terminus which comprises (i) one to eight sequential amino acids from the native amino acid sequence of the protein immediately C-terminal to said X or conservative substitutions in or modifications of said native amino acid sequence or   (ii) a substituent effective to facilitate coupling of the peptide to another moiety.       
     
     
       2. An article of manufacture for use in an immunoassay capable of detecting antibodies against meningitis-causing etiologic organisms or a chemokine involved in cell chemotaxis comprising a solid support and, having bound to said support, a peptide having a formula aXb according to claim 1.